Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue sarcomas of ectomesenchymal origin. The World Health Organization coined the term MPNST to replace previous heterogeneous and often confusing terminology, such as "malignant schwannoma," "malignant neurilemmoma," "neurogenic sarcoma," and "neurofibrosarcoma." Malignant peripheral nerve sheath tumors arise from major or minor peripheral nerve branches or sheaths of peripheral nerve fibers, and are derived from Schwann cells or pluripotent cells of neural crest origin. The Schwann cell is thought to be the major contributor to the formation of benign as well as malignant neoplasms of the nerve sheath. While this fact remains essentially true, the identity of cell of origin of the MPNST remains elusive, and has not yet been conclusively identified. It has been suggested that these tumors may have multiple cell line origins. In this review, the authors discuss the epidemiology, diagnosis, management, and treatment of MPNSTs.